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      Outcomes of both abbreviated hyper‐CVAD induction followed by autologous hematopoietic cell transplantation and conventional chemotherapy for mantle cell lymphoma: a 10‐year single‐centre experience with literature review

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          Abstract

          We retrospectively evaluated consecutive patients diagnosed with Mantle cell lymphoma ( MCL) between 01 January 2000 and 31 December 2009. Eighty eight patients with MCL were included in the analysis of whom 46 (52%) received abbreviated Hyper‐ CVAD (a total of two cycles; with addition of Rituximab since 2005) with an intention of proceeding to autologous hematopoietic cell transplantation (auto‐ HCT), with a median age of 58 years. Response rate to induction at auto‐ HCT time was 89% and complete response was 61%. Forty four patients received an auto‐ HCT with a 5‐year progression‐free survival ( PFS) and overall survival ( OS) were 31.2% and 62.5%, respectively. There were 42 nontransplant eligible patients with a median age of 72 years, and 5‐year PFS and OS were 0.0% and 39.9%, respectively. The median survival and PFS in the auto‐ HCT eligible group were 68 and 33 months, compared to 32 and 12 months in nontransplant eligible group, without a plateauing of the survival curves in either group. Treatment‐related mortality in the auto‐ HCT eligible group was 10.9% ( n = 5); two patients died during R‐Hyper‐ CVAD and 3 (6.8%) experienced transplant‐related mortality. An abbreviated R‐Hyper‐ CVAD‐based induction strategy followed by consolidative auto‐ HCT is feasible and provides moderate potential of long‐term survival. Further research to define risk‐adapted strategies; to optimize disease control, is required.

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          Most cited references25

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          Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group.

          Standardized guidelines for response assessment are needed to ensure comparability among clinical trials in non-Hodgkin's lymphomas (NHL). To achieve this, two meetings were convened among United States and international lymphoma experts representing medical hematology/oncology, radiology, radiation oncology, and pathology to review currently used response definitions and to develop a uniform set of criteria for assessing response in clinical trials. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients-especially those with large-cell NHL-who may not have residual disease. Single-photon emission computed tomography gallium scans are encouraged as a valuable adjunct to assessment of patients with large-cell NHL, but such scans require appropriate expertise. Flow cytometric, cytogenetic, and molecular studies are not currently included in response definitions. Response rates may be the most important objective in phase II trials where the activity of a new agent is important and may provide support for approval by regulatory agencies. However, the goals of most phase III trials are to identify therapies that will prolong the progression-free survival, if not the overall survival, of the treated patients. We hope that these guidelines will serve to improve communication among investigators and comparability among clinical trials until clinically relevant laboratory and imaging studies are identified and become more widely available.
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            A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group.

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              A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma.

              There is no generally established prognostic index for patients with mantle cell lymphoma (MCL), because the International Prognostic Index (IPI) and Follicular Lymphoma International Prognostic Index (FLIPI) have been developed for diffuse large cell and follicular lymphoma patients, respectively. Using data of 455 advanced stage MCL patients treated within 3 clinical trials, we examined the prognostic relevance of IPI and FLIPI and derived a new prognostic index (MCL international prognostic index, MIPI) of overall survival (OS). Statistical methods included Kaplan-Meier estimates and the log-rank test for evaluating IPI and FLIPI and multiple Cox regression for developing the MIPI. IPI and FLIPI showed poor separation of survival curves. According to the MIPI, patients were classified into low risk (44% of patients, median OS not reached), intermediate risk (35%, 51 months), and high risk groups (21%, 29 months), based on the 4 independent prognostic factors: age, performance status, lactate dehydrogenase (LDH), and leukocyte count. Cell proliferation (Ki-67) was exploratively analyzed as an important biologic marker and showed strong additional prognostic relevance. The MIPI is the first prognostic index particularly suited for MCL patients and may serve as an important tool to facilitate risk-adapted treatment decisions in patients with advanced stage MCL.

                Author and article information

                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                03 October 2015
                December 2015
                : 4
                : 12 ( doiID: 10.1002/cam4.2015.4.issue-12 )
                : 1817-1827
                Affiliations
                [ 1 ]Ottawa Hospital Blood and Marrow Transplant Program Ottawa OntarioCanada
                [ 2 ]College of Medicine at Taibah University Almadinah AlmunawarhSaudi Arabia
                [ 3 ] Department of Medical OncologyCancer Center KuwaitKuwait
                [ 4 ]Ottawa Hospital Research Institute Ottawa OntarioCanada
                Author notes
                [*] [* ] Correspondence

                Turki Abdulaziz Alwasaidi, College of Medicine, Taibah University, P. O. Box 51084, Almadinah Almunawarh, Saudi Arabia 41543. Tel: +966569179178; E‐mail: turkialwasaidi@ 123456hotmail.com

                Article
                CAM4543
                10.1002/cam4.543
                5123787
                26432256
                5c48eb66-ee09-435d-bbf4-8226342ada16
                © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 March 2015
                : 20 July 2015
                : 25 August 2015
                Page count
                Pages: 11
                Funding
                Funded by: Saudi Arabian Cultural Bureau in Canada
                Categories
                Original Research
                Clinical Cancer Research
                Original Research
                Custom metadata
                2.0
                cam4543
                December 2015
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.8 mode:remove_FC converted:25.11.2016

                Oncology & Radiotherapy
                autologous hematopoietic cell transplantation,conventional chemotherapy,mantle cell lymphoma,nontransplant eligible

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